Efficient methodology for the synthesis of 2-C-branched glyco-amino acids by ring opening of 1,2-cyclopropanecarboxylated sugars

An efficient methodology for the synthesis of 2-C-branched glyco-amino acid derivatives by diastereoselective ring opening of 1,2-cyclopropanecarboxylated sugars in good yields is reported. [reaction--see text]     

New lathyrane and podocarpane diterpenoids from Jatropha curcas

Chemical investigation on Jatropha curcas resulted in the isolation of twenty constituents among which four diterpenoids were unknown and six compounds, tetradecyl-(E)-ferulate, 3-O-(Z)-coumaroyl oleanolic acid, heudelotinone, epi-isojatrogrossidione, 2alpha-hydroxy-epi-isojatrogrossidione, and 2-methyanthraquinone had not been reported earlier from this species. The structures of the new compounds were established by extensive studies of their 1D- and 2D-NMR spectra.     

Discovery of Novel Coumarin Derivatives as Potential Dual Inhibitors against α-Glucosidase and α-Amylase for the Management of Post-Prandial Hyperglycemia via Molecular Modelling Approaches

Coumarin derivatives are proven for their therapeutic uses in several human diseases and disorders such as inflammation, neurodegenerative disorders, cancer, fertility, and microbial infections. Coumarin derivatives and coumarin-based scaffolds gained renewed attention for treating diabetes mellitus. The current decade witnessed the inhibiting potential of coumarin derivatives and coumarin-based scaffolds against α-glucosidase and α-amylase for the management of postprandial hyperglycemia. Hyperglycemia is a condition where an excessive amount of glucose circulates in the bloodstream. It occurs when the body lacks enough insulin or is unable to correctly utilize it. With open-source and free in silico tools, we have investigated novel 80 coumarin derivatives for their inhibitory potential against α-glucosidase and α-amylase and identified a coumarin derivative, CD-59, as a potential dual inhibitor. The ligand-based 3D pharmacophore detection and search is utilized to discover diverse coumarin-like compounds and new chemical scaffolds for the dual inhibition of α-glucosidase and α-amylase. In this regard, four novel coumarin-like compounds from the ZINC database have been discovered as the potential dual inhibitors of α-glucosidase and α-amylase (ZINC02789441 and ZINC40949448 with scaffold thiophenyl chromene carboxamide, ZINC13496808 with triazino indol thio phenylacetamide, and ZINC09781623 with chromenyl thiazole). To summarize, we propose that a coumarin derivative, CD-59, and ZINC02789441 from the ZINC database will serve as potential lead molecules with dual inhibition activity against α-glucosidase and α-amylase, thereby discovering new drugs for the effective management of postprandial hyperglycemia. From the reported scaffold, the synthesis of several novel compounds can also be performed, which can be used for drug discovery.     

Red-Light Activation of a Microtubule Polymerization Inhibitor via Amide Functionalization of the Ruthenium Photocage

Photoactivated chemotherapy (PACT) is a promising cancer treatment modality that kills cancer cells via photochemical uncaging of a cytotoxic drug. Most ruthenium-based photocages used for PACT are activated with blue or green light, which penetrates sub-optimally into tumor tissues. Here, we report amide functionalization as a tool to fine-tune the toxicity and excited states of a terpyridine-based ruthenium photocage. Due to conjugation of the amide group with the terpyridine π system in the excited state, the absorption of red light (630 nm) increased 8-fold, and the photosubstitution rate rose 5-fold. In vitro, red light activation triggered inhibition of tubulin polymerization, which led to apoptotic cell death both in normoxic (21 % O₂) and hypoxic (1 % O₂) cancer cells. In vivo, red light irradiation of tumor-bearing mice demonstrated significant tumor volume reduction (45 %) with improved biosafety, thereby demonstrating the clinical potential of this compound.     

Stereoselective Glycosylation of Glucosamine: The Role of the N‐Protecting Group

Oligosaccharides and glycoconjugates play an important role in biological processes. The use of these complex polymers as biocompatible materials for medicinal applications as well as therapeutic agents for the treatment of several diseases has attracted considerable interest. However, these investigations require large and pure amounts of glycostructures. Glucosamine is one of the major building blocks of these highly important glycoconjugates. Recently, considerable synthetic efforts have been devoted to improving stereoselective glycosylation. In this Focus review, the role of the amine protecting group in the outcome of the glucosamine glycosylation reaction is highlighted.     

Sulfoximines: a reusable directing group for chemo- and regioselective ortho C-H oxidation of arenes

Sulfoximines direct: a new protocol for the chemo- and regioselective ortho C-H acetoxylation of arenes in N-benzoylated sulfoximines is reported. The sulfoximine directing group is easily detached from the C-H oxidation product through acid-promoted hydrolysis, isolated, and reused. The meta-substituted phenols are synthesized following this strategy and the stereointegrity of the sulfoximine is preserved in this transformation. C(sp(3))-H acetoxylation of the methyl group is also demonstrated.     

Stereoselective synthesis of sugar fused β-disubstituted γ-butyro-lactones: C-spiro-glycosides from 1,2-cyclopropanecarboxylated sugars

A stereoselective methodology was developed for the construction of C-spiro-glycosides in two steps involving bromonium ion activated solvolytic ring opening of sugar derived 1,2-cyclopropanecarboxylates followed by a one-pot dehydrohalogenation, intramolecular hetero-Michael addition (IHMA) and ester hydrolysis. The obtained spirocyclic lactols were further converted to enantiomerically pure spirolactones.     

Polymer Embedded Nanocrystalline Titania: A New Generation Sorbent for the Separation of 77As from Ge for Biomedical Applications

The present work demonstrates the utility of polymer embedded nanocrystalline titania (TiP) as a new, accessible and viable solid sorbent for the chromatographic separation of high specific activity ⁷⁷As from neutron irradiated natural GeO₂. Experimental parameters such as distribution ratios (K _d), equilibrium sorption capacity, breakthrough capacity and separation yields were determined. A two-step ion-exchange procedure was developed to avail ⁷⁷As, from irradiated Ge in alkaline medium. The first step involved removal of the bulk Ge from ⁷⁷As by selective sorption of Ge ions on a TiP column at pH 13. Subsequently, the effluent solution containing ⁷⁷As was further purified and concentrated by sorption on a small TiP column at pH 10. ⁷⁷As could be eluted from the second column in 2?C3?mL of 0.1?M NaOH solution with >80% radiochemical yield. The ⁷⁷As obtained by this method was found to have insignificantly small level of radiocontaminants.     

Selective complexation of alkali metal ions using crown ethers derived from calix[4]arenes: a computational investigation of the structural and energetic factors

A systematic analysis of the structural, energetic, and thermodynamic factors involved in alkali metal (i.e., Na⁺, K⁺, Rb⁺, and Cs⁺) complexation by four calix[4]arene crown-6 ethers in the 1,3-alternate conformation is presented here. The ligands (or hosts) in this work are identical to, or closely related to, the four molecules whose selectivity towards complexing Na⁺, K⁺, Rb⁺, and Cs⁺ from aqueous solutions was studied experimentally by Casnati et al. (Tetrahedron 60(36):7869–7876, 2004). By dividing the complexation process into three different contributions, namely, the binding energy of the ion to the crown, the elastic energy of the crown, and the solvation effect, it becomes clear that the primary factor that determines ion selectivity in crown-6-ethers is not the size of the crown, as currently believed. All four crown ethers preferentially complex with the smallest ion (Na⁺) in the gas phase. In the condensed phase, these crown-6 ethers preferentially complex with the larger ions only because the aqueous solvation energies of the alkali metal ions make it thermodynamically less favorable to extract the smaller ions from aqueous solutions. This suggests that the current understanding of the factors influencing the selectivity of metal ion complexation by crown ethers may be in need of revision.     

Synthesis and characterization of ammonium molybdophosphate–silica nano-composite (AMP–SiO2) as a prospective sorbent for the separation of 137Cs from nuclear waste

The ammonium molybdophosphate–silica (AMP–SiO₂) nano-composites were prepared by sol–gel method. The material synthesized was nanocrystalline, with average crystallite size of primary particles in the range of 10–25 nm. Small angle X-ray scattering showed presence of mass fractal aggregates made of small particles with rough pore boundaries. To realize the scope of using AMP–SiO₂ nano-composites sorbent for removal of ¹³⁷Cs from nuclear waste solutions, its adsorption characteristics for cesium were evaluated. It was found that the AMP–SiO₂ nanocomposites were amenable for column operation, have high affinity for Cs, and possess very high adsorption capacity for Cs. From the perspective of separation of ¹³⁷Cs from acidic radioactive waste solution, AMP–SiO₂ nanocomposite holds significant promise.